| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Outline of Final Research Achievements |
We previously reported that macrolide antibiotics including clarithromycin (CAM) have an inhibitory effect on autophagy flux, and combined treatment with a proteasome inhibitor bortezomib (BZ) leads to enhanced apoptosis induction via endoplasmic reticulum (ER) stress overloading in multiple myeloma (MM) cells. Since bone marrow microenvironment supports the myeloma cell growth and induces cell adhesion-mediated drug resistance (CAM-DR), we investigated the cytotoxic effect of BZ plus macrolide combination using the co-culture system of EGFP-labelled MM cell lines and stroma cell lines. EGFP-MM cells were charged onto the stroma cell monolayer and co-cultured with BZ in the presence or absence of macrolide. We have observed that the pronounced BZ-induced cytotoxicity by macrolide in MM cells co-cultured on the stroma layer. These data suggest that macrolide could be used as an autophagy inhibitor and combined treatment with BZ plus macrolide can be overcome CAM-DR.
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